Colonic Carcinoma

History

Fact

Explanation

Pattern of presentation

Colon cancer is a common malignancy worldwide and is especially common among the elderly.[1] In the United States it is the third common malignancy among both men and women.[2] Majority are adenocarcinomas. The presentation differs according to the site of the tumor and macroscopic variety. Colon cancer is more common in the left side and these tumors tend to present earlier with features of intestinal obstruction. Right sided tumors present late with anemia or abdominal mass. Annular lesions present with intestinal obstruction. Ulcerative, tubular and cauliflower varieties mainly present with intestinal bleeding.

Tumors of the descending colon and sigmoid colon present with increasing intestinal obstruction. The solid nature of the fecal matter and the thick abdominal walls predispose to obstruction. The patient may present acutely with complete intestinal obstruction. Peritonitis is a rare complication resulting from extensive peritoneal metastasis. The tumor may act as the apex for intussusception and present with intermittent colicky abdominal pain, constipation and abdominal distension.

Per-rectal bleeding

Bleeding from higher lesions lead to formation of altered blood which is mixed within the stool. Lower lesions present with bright red bleeding.

Features of anemia

Iron deficiency anemia develops due to chronic blood loss. This is a common symptom of tumors within the cecum and ascending colon.

Abdominal mass

Patients may detect a lump in the right iliac fossae. A tumor of the transverse colon usually is felt in the epigastric region.

Alteration of bowel habits

Patients may present with both constipation and diarrhea. It is important to first identify the patient’s previous bowel habits.

Tenesmus, feeling of incomplete evacuation

These are characteristic features of a low lying tumor in close proximity to the rectum - sigmoid colon tumors. In addition they may present with spurious diarrhea with passage of mucus.

Features due to local spread

Local invasion into the bladder may cause urinary symptoms - frequency, urgency, recurrent urinary tract infections. This may result in a colovesical fistula.

Features due to distant spread

Features of metastatic spread may be the patients' initial presentation. Hematogenous spread is usually to the liver, lung and rarely to the brain or bones. Liver metastases are present with right hypochondrial pain, severe anorexia and jaundice. Lung metastases give rise to chronic cough, haemoptysis and dyspnea.

Risk factors/ Associations

Both genetic and environmental factors have being implicated in the pathogenesis of colonic carcinoma. Look for a family history especially in younger patients. Adenoma-carcinoma sequence describe the transition of benign adenomas into malignancy due to progressive accumulation of genetic mutations.[3] A lower fiber diet has being shown to increase the risk of colon cancer. The bulk of the fecal matter is reduced resulting in an increased colon transit time. Hence the mucosa is exposed to carcinogens for an increased time duration. High consumption of red meat and saturated fat products has also being linked with increased risk of colon cancer. Long standing ulcerative colitis increases the risk of colon cancer.[4]

Examination

The tumor induces a catabolic state. In addition there may be loss appetite due to secretion of varies chemical mediators.

Abdominal examination : Abdominal mass

In advanced disease an intra-abdominal mass may be palpable. The site of the mass is determined by the location of the tumor within the colon. The mass is usually hard in consistency, consists of an irregular surface and may have restricted mobility due to fixation to surrounding structures.

Abdominal examination : Hepatomegaly

Due to liver metastasis.

Abdominal examination : Ascites

Due to infiltration of the peritoneum by the tumor. Carcinomatosis peritonei results from extensive transcoelomic spread.[1]

Rectal examination : Usually normal

Sigmoid colon tumors are rarely palpable per rectally. A low lying recto-sigmoid tumor will be palpable as a hard mass which has an irregular surface and may have restricted mobility due to fixation. Note the distance of the tumor from the anal verge.

Differential Diagnoses

Fact

Explanation

Benign tumors of the colon

Polyps found within the colon could be of inflammatory, metaplastic, harmartomatous or neoplastic. Benign adenomatous polyps may be single or multiple - polyposis. Tubular adenoma are usually asymptomatic or may cause per rectal bleeding. Villous adenoma are usually hyper-secretive causing diarrhea, mucus discharge and may even cause hypokalaemia. Adenomas over time may turn into malignant lesions, the risk is high with larger size and villous morphology. Colonoscopy is required for diagnosis and small lesions can be removed via the endoscope. Rarely larger high risk lesions may require proctectomy.

Familial adenomatous polyposis (FAP)

FAP is an autosomal dominant condition due to mutations in the APC gene. A majority of patients have a strong family history for FAP, while in some it may arise due to new mutations. Over 100 polyps are found within the colon and may also be present within the stomach, duodenum and jejunum. These adenomatous polyps carry a significant risk of malignant transformation. FAP accounts for 1% of all colorectal carcinomas. Polyps appear at a young age (15-20yrs) and may turn into malignant lesions if left unidentified for 10-20 yrs. Most patients are screened regularly by surveillance programs and are identified when still asymptomatic. Symptomatic patients present late with diarrhea which may contain blood/ mucus, abdominal pain, weight loss etc. Physical examination is usually normal. Diagnosis is by colonoscopy/ sigmoidoscopy and biopsy of suspicious lesions. Screening policies are adopted to identify high risk individuals early. The standard surgical treatment is colectomy with creation of an ileorectal anastomosis.[1]

Ulcerative Colitis

Ulcerative Colitis is a chronic inflammatory disease affecting the colonic mucosa. This relapsing and remitting systemic condition mainly affects the young - 15 to 30 yr age group. The aetiology is unknown. The inflammatory reaction is limited to the superficial layers of the colon. It initially affects the rectum (proctitis) and may spread proximally to involve the sigmoid colon (sigmoproctitis) or the whole colon (pancolitis). The presentation is with abdominal pain, weight loss and diarrhea which may contain blood and mucus. Tenesmus, urgency and mucoid diarrhea are features of rectal disease. Acute attacks are characterized by fever, anorexia, malaise and weight loss. Extra-intestinal features - oral ulcers, conjunctivitis, clubbing, skin rashes- eryhtema nodosum & pyoderma gangrenosum. Physical examination is usually normal. Complications of ulcerative colitis - Bowel perforation, bleeding, toxic dilatation of colon. The colonic cancer risk is increased in patients with longstanding pancolitis. Diagnosis is by clinical information supported by visualization of the colon by sigmoidoscopy or colonoscopy. Rectal biopsy is required for histological analysis.[2]

Crohn's disease

Crohn's disease is part of the disease spectrum of inflammatory bowel disease. It can affect the whole gastrointestinal tract from mouth to anus but predominantly affects the terminal ileum, proximal colon and the jejunum. The inflammatory reaction characteristically involves the whole abdominal wall. Areas of active disease is interrupted by non-affected areas (skip lesions). Ulceration of the bowel is common and may progress to fistula formation. Fistulae may form between bowel loops or between bowel and bladder, vagina and in the anal region. The disease presents with chronic abdominal pain, diarrhea, weight loss and per rectal bleeding. Systemic symptoms such as fever, anorexia and malaise may be present. On physical examination right iliac fossa mass, perianal abscesses and fistulae may be found. Extra-intestinal features include clubbing, episcleritis, conjunctivitis, large joint arthritis and skin lesions. Diagnosis again requires colonoscopic assessment with biopsy of affected regions.[3]

Investigations - for Diagnosis

Fact

Explanation

Colonoscopy

Colonoscopy is the investigation of choice for investigating patients suspected of colonic carcinoma. Following bowel preparation colonoscopy is used to visualize the whole colon up to the ileo-caecal valve. If a tumor is detected multiple biopsies are taken for histological analysis. The added advantages of colonoscopy are the ability to exclude multiple carcinomas and synchronous polyps. Synchronous tumors are found in 3.8 to 5% of patients diagnosed with colonic carcinoma. They are more commonly found in men and patients aged over 65yrs.[1]

Sigmoidoscopy

Sigmoidoscopy can used to diagnose tumors in the sigmoid colon. The advantage of sigmoidscopy is that it could be done as an out-patient procedure without anesthesia. Proximal benign or malignant tumors are missed if sigmoidoscopy alone is used.

Double contrast barium enema

Enema can be used if colonoscopy is inconclusive or contraindicated. The tumor appears as a constriction or filling defect.[2] Flat infiltrating tumors may be missed by barium studies.

Spiral CT

Spiral CT can be used if standard investigations such as colonoscopy and barium study is inconclusive. With the advancing technology in spiral CT of virtual visualization of the colon, spiral CT is increasingly being used in certain centers.[3]

Investigations - Fitness for Management

Prior to undergoing major surgery patients’ fitness for surgery needs to be assessed. FBC is needed to determine the hemoglobin level.

Blood urea/ Serum electrolytes

To assess renal functions.

Liver function tests

To assess liver functions.

ECG/ Echocardiography

Assess cardiovascular functions if surgery is considered.

Blood grouping and save

Reserve blood prior to surgery.

References

Investigations - Screening/Staging

Fact

Explanation

Staging of colon carcinoma

Staging is done according to the Tumor-Node-Metastasis classification. Information gathered by both physical examination and investigation is used for staging. The T stage is determined by the degree of tumor invasion through the colonic wall. N stage represents the lymph node involvement. M stage represents distant metastasis.

Ultrasound scan

USS can be used to screen for liver metastases. Presence of free fluid in the abdomen may suggest peritoneal infiltration.

CT Abdomen

CT scan of the abdomen and pelvis can be used to investigate for local infiltration and lymph node enlargement.[1] [2]

Management - General Measures

Fact

Explanation

Patient education and counseling

The diagnosis of colon cancer should be revealed to the patient and family sensitively. Provide information regarding the site & severity of the lesion, complications and investigations required. Counsel the patient regarding the prognosis and available treatment options.

Multi-disciplinary care

The most appropriate management plan should be decided with the input of surgeons, gastroenterologists, oncologists, pathologists and nursing staff. Refer the patient to a stoma care nursing specialist for assessment and planning of stoma placement.

Provide psychological support

The patient and family members may be distressed following diagnosis of cancer.

Optimization prior to surgery

If surgery is planned, medical conditions should be optimized prior to surgery. Anemia needs to be corrected with either iron supplementation or blood transfusion. Achieve adequate control of blood glucose and blood pressure.

Antibiotics are administered at the time of induction to minimize the risk of infection. A single dose of intravenous antibiotics is considered sufficient.[1]

Prevention of deep vein thrombosis

Patients with malignancy have an increased tendency for venous thrombosis. Prolonged immobilization following radical surgery may further increase the risk.[2] Adequate hydration, leg movements, compression stockings and anti-coagulants- Heparin are used to prevent DVT. Early mobilization is encouraged after satisfactory recovery.

Screening of relatives of FAP

Genetic screening for mutations of the APC gene in relatives of the patient can help identify high risk patients. These patients require continuously follow up form a young age with annual sigmoidoscopy. In high risk patients prophylactic colectomy may be offered to prevent colorectal carcinoma.[3]

Hereditary nonpolyposis colorectal cancer

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant condition resulting from mutations of the DNA mismatch repair genes. These patients are at a higher risk of varies cancers - Colorectal, urothelial, endometrial and ovarian cancers. Amsterdam criteria are used to diagnose patients with HNPCC. The criteria cited assess the presence of associated carcinoma among family members, the affected age and the pathology of the cancers. Patients presenting with colon cancer with strong family history need to be evaluated for both FAP and HNPCC.

Management - Specific Treatments

Fact

Explanation

Treatment options

Treatment options should be decided based on the stage of the tumor, patient fitness for surgery and patient wishes. The treatment of choice is curative resection of the tumor. Some form of resection is advocated in all patients even in widely metastatic disease as a palliative measure.[1]

Surgery

The primary aim of surgery is to remove the tumor mass along with its draining lymph nodes. Laparotomy is performed and assessment is carried out to determine resectability. The surgeon inspects the site of the tumor for local infiltration. Next the draining lymph nodes are examined for enlargement. Lymphadenopathy may be even be reactive due to inflammation. The peritoneum and the omentum are systematically inspected for tumor deposits. Peritoneal washings are collected for cytology. The liver is examined for liver metastases. The tumor is resected en bloc with tumor free margins and lymphadenecyomy is performed. Specimens are sent for histopathological analysis. If inoperable malignancy is found a less radical resection can be made for palliation. Laparoscopic surgery has being tried in certain situations. It has found to be safe, efficacious and reduces the hospital stay while shortening the time needed for healing. Advanced expertise and facilities are required and the surgical procedure is more difficult. Further evaluation is required.[2]

Surgical procedure is determined by the site of the tumor

Tumors situated within the cecum and ascending colon are removed by right hemicolectomy. This procedure needs to extended further towards the transverse colon if the tumor is located in the hepatic flexure. Transverse colon tumors are removed by resection of the transverse colon and the hepatic and splenic flexures. Extended left hemicolectomy is performed if the tumor is located in the splenic flexure or descending colon. A pancolectomy with ileorectal anastomosis is performed if the tumor is extensively spread. Carcinoma of the sigmoid colon requires resection from the splenic flexure up to the upper third of the rectum.

Restoring continuity of the large bowel

Primary anastomosis is the preferred option. End to end anastomosis is performed if the resected margins are tumor free and are adequately perfused. A temporary de-functioning anastomosis is used to improve healing in certain situations.

Managing inoperable tumors

These patients often require a permanent stoma. A by-pass surgery can be performed for right sided tumors. Ileostomy is performed for left sided tumors while a permanent colostomy in the left iliac fossa is used for low lying tumors. Monoclonal antibodies have shown promise in treatment of metastatic disease.[3]

Chemotherapy

Cytotoxic drugs are used in advanced tumors with wide spread hematogenous metastasis. Presence of multiple hepatic metastases is an indication for chemotherapy.

Management of hepatic metastases

New evidence suggests improved survival rates following hepatic resection of secondary deposits.[4] Combination with systemic chemotherapy has being shown to prolong this effect. The site and number of deposits are determined by radiological imaging. Hepatectomy can be performed in patients who have less than 3 secondaries per liver lobe.[5]

Management of acute large bowel obstruction

Initial resuscitation is performed with correction of fluid & electrolyte imbalances, pain relief and gastrointestinal drainage. The patient is kept nil by mouth. Laparotomy is performed and the bowel is traced to identify the cause. The affected segment is removed en bloc. The proximal dilated bowel is decompressed and anastomosis may be considered. If the lesion is inoperable a stoma or bypass surgery is performed.